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Aligning multiple genomic sequences with the threaded blockset aligner.

We define a "threaded blockset," which is a novel generalization of the classic notion of a multiple alignment. A new computer program called TBA (for "threaded blockset aligner") builds a threaded blockset under the assumption that all matching segments occur in the same order and orientation in the given sequences; inversions and duplications are not addressed. TBA is designed to be appropriate for aligning many, but by no means all, megabase-sized regions of multiple mammalian genomes. The output of TBA can be projected onto any genome chosen as a reference, thus guaranteeing that different projections present consistent predictions of which genomic positions are orthologous. This capability is illustrated using a new visualization tool to view TBA-generated alignments of vertebrate Hox clusters from both the mammalian and fish perspectives. Experimental evaluation of alignment quality, using a program that simulates evolutionary change in genomic sequences, indicates that TBA is more accurate than earlier programs. To perform the dynamic-programming alignment step, TBA runs a stand-alone program called MULTIZ, which can be used to align highly rearranged or incompletely sequenced genomes. We describe our use of MULTIZ to produce the whole-genome multiple alignments at the Santa Cruz Genome Browser.

Animals↗

Techniques for perfusion imaging with microbubble contrast agents.

The acoustic properties of ultrasound contrast agents vary widely with agent composition and insonation conditions. For contrast imaging, methods are required to match RF and Doppler processing to each combination of transmission parameters and agent and tissue properties. We propose a method that uses the measured or modeled echoes from agent and tissue to specify directly the characteristics of RF and Doppler filters for contrast imaging. The proposed method is sufficiently general to cover most common imaging techniques including harmonic greyscale, Doppler, and pulse inversion imaging. Using this method, sample filters were designed to detect myocardial perfusion with the contrast agent Optison (Mallinckrodt Medical, St. Louis, MO) under selected imaging conditions. Simplified power Doppler filtering, using a weighted sum of the Doppler samples, matched the performance of more complicated matrix filters. By coordinating the selection of RF and Doppler filters rather than designing these filters sequentially, agent-to-tissue contrast was increased by up to 3.9 dB. Under some conditions, fundamental RF filtering outperformed harmonic filtering for intermittent Doppler imaging.

Contrast Media↗

The effect of left ventricular intracavitary volume on the unipolar electrogram.

In order to examine the effects of ventricular distention on the unipolar electrogram (UEG), an isolated rabbit heart modified Langendorff preparation was utilized. Left ventricular (LV) volume was adjusted using ionically permeable (PB = 9 hearts) or ionically impermeable balloons (IB = 4 hearts). LV UEGs, LV end-diastolic pressure (EDP), and LV minor axis dimension (MAD), as measured by ultrasonic transducers, were recorded. Three hundred twenty-five electrograms were digitized and analyzed with custom-designed software. In the PB group, a significant inverse linear relationship was found between UEG amplitude and changes in MAD (P < 0.0001). For each animal, this relationship had an R value > 0.8 and a P value < 0.0001. There was also a significant inverse linear relationship between UEG slope and changes in MAD (P < 0.01). UEG amplitude and slope also exhibited a significant inverse relationship to changes in LV EDP, which were best described by a third order polynomial function. In the IB group, no significant relationship was found between either UEG amplitude or slope and MAD or EDP. In this study, intracavitary volume exerted a profound and significant influence on UEG amplitude and slope. This effect was due to increases in conductive intraventricular volume and not to myocardial stretch.

Animals↗

CyberKnife radiotherapy for localized prostate cancer: rationale and technical feasibility.

There is a clear dose response for localized prostate cancer radiotherapy and there probably is a radiobiological rationale for hypo-fractionation. Combining the two should maximize tumor control and increase the therapeutic ratio. This study examines the rationale and technical feasibility of CyberKnife radiotherapy (a robotic arm-driven linear accelerator) for localized prostate cancer. Its ability to deliver non-coplanar non-isocentric arcs can yield maximally conformal isodoses. It is the only integrated system capable of target position verification and real-time tracking during delivery of conformal stereotactic radiotherapy. Inverse planning with the CyberKnife is used to design a course of radiotherapy for localized prostate cancer. Fiducial markers within the gland are used to verify organ position and track organ motion via an orthogonal pair of electronic x-ray imaging devices and provide real-time feedback correction to the robotic arm during delivery. Conformal isodose curves and dose volume histograms (DVH) are used to compare with an optimized Intensity-Modulated Radiotherapy (IMRT) plan actually delivered to the study patient based upon CT scan-derived organ volumes. The CyberKnife can produce superior DVHs for sparing of rectum and bladder and excellent DVHs for target coverage compared with IMRT, and possesses dose heterogeneities to the same degree as IMRT plans. Because of the significantly longer delivery times required it would be best suited for hypo-fractionated regimens. Such dose regimens might allow for biologically equivalent dose escalation without increased normal tissue toxicity. Since the CyberKnife can verify organ position and motion and correct for this in real-time it is the ideal means of achieving such excellent DVHs without a compromise in doses to normal tissues. These capabilities are essential if one contemplates hypo-fractionated regimens with large dose-per-fraction sizes (>5Gy to 10Gy) and dose-escalation.

Equipment Design↗

Factors related to glycemic control in IDDM and insulin-treated NIDDM patients in current practice. A comparison of care policies. SIEMTIC Group. Studio Italiano Epidemiologico Multicentrico su Terapia Insulin e Controllo Metabolico.

OBJECTIVE: To evaluate, under routine conditions, the relation between different diabetes care policies and glycemic control through a by-center analysis procedure aimed at reducing some drawbacks of cross-sectional data. RESEARCH DESIGN AND METHODS: A survey on insulin-treated diabetes care management (IDDM and NIDDM) involved 16 Italian randomly selected diabetes outpatient clinics. A total of 2,142 representative patients were investigated. The standardized HbA1c average value of each center was related, by regression models, to some indicators of center care policy (average number of injections, average BMI, proportion of cases with recent fundus oculi examinations, or frequent visits) as well as to patients' average social levels (employment type). Homogeneity in patient admission criteria is assumed among the investigated centers as a basic condition for the procedure validity. Some known imbalance were controlled for both design and analysis. RESULTS: HbA1c showed a univariate inverse relation with daily number of injections in IDDM (P = 0.0009, r2 = 0.56) but not in NIDDM (P = 0.33). It was inversely related to both fundus examination (IDDM P = 0.04; NIDDM P = 0.099) and qualified employment (IDDM P = 0.06; NIDDM P = 0.026). A stepwise regression analysis left in the model insulin injections (P = 0.0002) in IDDM (total r2 = 0.68) and qualified employment (P = 0.016) and fundus examination (P = 0.14) in NIDDM (total r2 = 0.53), after controlling for age, sex, disease duration, insulin therapy starting delay, and insulin dose per kilogram. CONCLUSIONS: These results suggest that the confirmed benefits of a multiple-injection regimen in IDDM cannot be simply extrapolated to NIDDM, where patients' awareness and medical attention to complications proved to be the most important factors in current practice.

Adult↗

Electromyographic response of peroneal muscles in surgical and nonsurgical injured ankles during sudden inversion.

Because the peroneal muscles are thought to act as a safeguard against lateral ankle injury, it is important to study their function. This study was undertaken to electromyographically assess the latency between sudden unexpected ankle inversion and the start of peroneal muscle activity. Three groups participated in the study, including subjects with lateral ankle sprain rehabilitated nonsurgically (N = 7), sprains rehabilitated following surgery (N = 6), and injury-free ankles (N = 11). Peroneal latency was assessed by dropping the subjects into inversion from a special platform. The platform was designed so that either ankle could be inverted to 35 degrees without warning. The ANOVA revealed no significant latency differences (p > .05) between the three groups. The study suggests that bilateral peroneal latency is unaffected by injury. Although it has been thought that healthy muscles provide a defense against ankle sprain, their latency is not permanently affected by ankle injury or by surgery performed to correct defects from injury. It appears that mechanoreceptor impairment may be rehabilitated and that it is not a factor in ankle injury.

Adolescent↗

Alcohol consumption and risk for coronary heart disease among men with hypertension.

BACKGROUND: Heavy alcohol consumption increases risk for hypertension, which is in itself a strong risk factor for cardiovascular disease (CVD). However, data on the association between alcohol consumption and CVD among individuals with hypertension are scarce. OBJECTIVE: To assess whether alcohol consumption is inversely associated with CVD among men with hypertension. DESIGN: Prospective cohort study. SETTING: United States. PARTICIPANTS: 11,711 men with hypertension from the Health Professionals Follow-Up Study. MEASUREMENTS: Alcohol consumption was assessed every 4 years by using a food-frequency questionnaire. Incident cases of nonfatal myocardial infarction (MI), fatal coronary heart disease, and stroke were documented from 1986 to 2002. RESULTS: During follow-up, 653 patients with MI were documented. Compared with patients abstaining from alcohol, the hazard ratio for participants with MI consuming 0.1 to 4.9 grams of alcohol per day was 1.09 (95% CI, 0.86 to 1.37); consuming 5 to 9.9 grams of alcohol per day was 0.81 (CI, 0.60 to 1.08 g/d); consuming 10 to 14.9 grams of alcohol per day was 0.68 (CI, 0.51 to 0.91 g/d); consuming 15 to 29.9 grams of alcohol per day was 0.72 (CI, 0.54 to 0.97 g/d); consuming 30 to 49.9 grams of alcohol per day was 0.67 (CI, 0.48 to 0.94 g/d); and consuming 50 or more grams of alcohol per day was 0.41 (CI, 0.22 to 0.77 g/d) (P < 0.001 for trend). Associations were similar for fatal and nonfatal MI. Alcohol consumption was not associated with total death or death due to CVD. Risks for total and ischemic stroke for patients consuming 10 to 29.9 g of alcohol per day were 1.40 (CI, 0.93 to 2.12) and 1.55 (CI, 0.90 to 2.68) compared with that of abstainers. When corrected for measurement error in alcohol consumption, dietary variables, and body mass index, the hazard ratio for participants with MI per 12.5 grams per day increment of alcohol intake was 0.68 (CI, 0.46 to 1.00). LIMITATIONS: Hypertension, alcohol consumption, and CVD risk factors were assessed by self-report. Available data used to correct for measurement error were primarily restricted to dietary variables. CONCLUSIONS: In this population of men with hypertension, moderate alcohol consumption was associated with a decreased risk for MI but not with risks for total death or death due to CVD. As in the general population, men with hypertension who drink moderately and safely may not need to change their drinking habits.

Adult↗

Structure and evolution-guided design of minimal RNA-guided nucleases.

The design of RNA-guided nucleases with properties not limited by evolution can expand programmable genome-editing capabilities. However, generating diverse multidomain proteins with robust enzymatic properties remains challenging. Here, we use a protein design strategy that couples a structure-guided inverse-folding model with evolution-informed residue constraints to generate active, divergent variants of TnpB, a minimal CRISPR-Cas12-like nuclease, termed SynTnpBs. High-throughput screening of artificial intelligence-generated variants yielded editors that retained or exceeded wild-type activity in bacterial, plant, and human cells. Cryo-electron microscopy-based structure determination of the most divergent variant revealed stabilizing contacts in the RNA-DNA interfaces across conformations, demonstrating the design potential of this approach. Together, these results establish a strategy for creating non-natural RNA-guided nucleases and conformationally active nucleic acid binders, enlarging the designable protein space.

Humans↗

Clinical implication of left precordial T wave inversions in the presence of complete right bundle branch block.

This study was designed to elucidate whether left precordial negative T waves are electrocardiographic indicators for the diagnosis of hypertrophic cardiomyopathy (HCM) even in the presence of complete right bundle branch block (CRBBB). In 7 consecutive patients with CRBBB accompanied by negative T waves in at least one of the left precordial leads (V4, V5, V6, maximal negativity; 1.06 +/- 0.40 mVol) (left precordial negative T wave group) and in 15 randomly selected CRBBB patients without left precordial T wave inversions (control group), echocardiography was performed to rule out underlying diseases causing left ventricular overload and to identify candidates for magnetic resonance (MR) imaging. None had anginal pain indicating ischemic heart disease. When 2-dimensional echocardiography indicated left ventricular hypertrophy with wall thickness > or = 15 mm, the magnitude and distribution of hypertrophy were scrutinized on contiguous left ventricular MR short-axis images. The diagnostic criterion of HCM was the demonstration of hypertrophy with a wall thickness of 20 mm or more on the left ventricular MR short-axis images. All patients in the left precordial negative T wave group had negative T waves in both I (negativity; 0.27 +/- 0.17 mVol) and aVL (negativity; 0.23 +/- 0.14 mVol), whereas none in the control group did. The diagnostic criterion for HCM was fulfilled in six patients in the left precordial negative T wave group. However there were no patients who fulfilled the criterion in the control group. Negative T waves were recorded in the I (negativity; 0.30 +/- 0.17 mVol), aVL (negativity; 0.25 +/- 0.14 mVol), V4 (negativity; 1.03 +/- 0.46 mVol), V5 (negativity; 0.83 +/- 0.37 mVol) and V6 leads (negativity; 0.31 +/- 0.31 mVol) in all patients with HCM, while they were recorded in only 6% of the patients without HCM. In conclusion, the existence of left precordial negative T waves in the presence of CRBBB strongly indicates HCM.

Bundle-Branch Block↗

Multiple inverted DNA repeats of Bacteroides fragilis that control polysaccharide antigenic variation are similar to the hin region inverted repeats of Salmonella typhimurium.

The important opportunistic pathogen Bacteroides fragilis is a strictly anaerobic Gram-negative bacterium and a member of the normal resident human gastrointestinal microbiota. Our earlier studies indicated that there is considerable within-strain variation in polysaccharide expression, as detected by mAb labelling. Analysis of the genome sequence has revealed multiple invertible DNA regions, designated fragilis invertible (fin) regions, seven of which are upstream of polysaccharide biosynthesis loci and are approximately 226 bp in size. Using orientation-specific PCR primers and sequence analysis with populations enriched for one antigenic type, two of these invertible regions were assigned to heteropolymeric polysaccharides with different sizes of repeating units, as determined by PAGE pattern. The implication of these findings is that inversion of the fin regions switches biosynthesis of these polysaccharides off and on. The invertible regions are bound by inverted repeats of 30 or 32 bp with striking similarity to the Salmonella typhimurium H flagellar antigen inversion cross-over (hix) recombination sites of the invertible hin region. It has been demonstrated that a plasmid-encoded Hin invertase homologue (FinB), present in B. fragilis NCTC 9343, binds specifically to the invertible regions and the recombination sites have been designated as fragilis inversion cross-over (fix) sites.

Antigenic Variation↗

The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice.

Non-agouti-lethal 18H (a18H) mice are dark agouti with black pinna hairs. What makes these mice unique is that they develop a spectrum of immunological diseases not seen in other agouti mutant mice. On the JU/Ct background, a18H mice develop an inflammatory disease of the large intestine. On the C57BL/6J background, they develop a fatal disease characterized by pulmonary chronic interstitial inflammation and alveolar proteinosis, inflammation of the glandular stomach and skin resulting in scarring due to constant itching, and hyperplasia of lymphoid cells, haematopoietic cells and the forestomach epithelium. Previous studies suggested that the a18H mutation results from a paracentric inversion that affects two loci: agouti and another, as yet unidentified locus designated itchy (the provisional gene symbol is Itch), that is responsible for the immunological phenotype of a18H mice. Here we confirm that a18H results from an inversion and show that Itch encodes a novel E3 ubiquitin protein ligase, a protein involved in ubiquitin-mediated protein degradation. Our results indicate that ubiquitin-dependent proteolysis is an important mediator of the immune response in vivo and provide evidence for Itch's role in inflammation and the regulation of epithelial and haematopoietic cell growth.

Amino Acid Sequence↗

Digital scintigraphy: principles, design, and performance.

In a digital camera the position of a scintillation event is computed following analog-to-digital conversion of photomultiplier pulse charges. Digital position analysis is essentially a mathematical inversion procedure based upon calibrated responses of the photomultipliers to scintillations from a narrow-beamed source that maps a detector's field of view. Operationally, a camera's image characteristics are optimized by means of computer-generated inversion reference tables, individually tailored to the specific response characteristics of each detector. Design considerations indicate that cameras of varied configurations, e.g., linear, disc-shaped, rectangular, or cylindrical, can be analyzed by this method. Also, for any given electro-optical system, energy resolution, spatial characteristics, and event-rate performance can be made superior to analog systems. The measured performances of a one-dimensional test camera, although limited in its optical and electronic design, support this conclusion.

Analog-Digital Conversion↗

Percolation testing and hydraulic conductivity of soils for percolation areas.

The results of specific percolation tests are expressed in terms of field saturated hydraulic conductivity (Kfs) of the soil. The specific tests comprise the Irish SR 6 and the UK BS 6297 standard tests and the inversed auger hole and square hole tests employed for the design of land drainage. Percolation times from these tests are converted to Kfs values using unit gradient theory and the Elrick and Reynolds (Soil Sci. 142(5) (1986) 308) model which takes into account gravitational, pressure head and matric potential gradients. Kfs is then expressed as the inverse of the percolation rate times a constant, in this way the percolation rate can be directly related to Kfs of the soil. A plot of Kfs against percolation rate for the Irish SR 6 and the UK BS 6297 standard tests is asymptotic at Kfs values less than 0.2 m/d and greater than 0.8 m/d. This behaviour creates difficulty in setting limits for percolation rates in standards. Curves are provided which enable Kfs values to be read off from percolation tests without the restrictions of head range currently enforced, for example in the Irish SR 6 and BS 6297 standards. Experimental measurements of percolation rates and Kfs were carried out on two sands in the laboratory and in the field on two soils. Kfs of these four materials was also measured using a tension infiltrometer and the Guelph permeameter. The saturated hydraulic conductivities (Ks) of the sands were also estimated in a falling head laboratory apparatus and by the Hazen formula. There was good agreement between the different tests for Kfs on each material. Because percolation time continued to increase significantly in consecutive tests in the same test hole while Kfs became constant, the latter is a better measure of the suitability of soils for percolation.

Models, Theoretical↗

Magnetic resonance imaging of normal and osteomyelitis in the mandible: assessment of short inversion time inversion recovery sequence.

OBJECTIVE: We sought to determine the suitable magnetic resonance imaging conditions for the short inversion time inversion recovery (STIR) sequence through the use of phantoms; to describe the signal characteristics of normal structures in the mandible; and to evaluate the usefulness of STIR images in enabling the identification of mandibular osteomyelitis on conventional T1- and T2-weighted spin-echo images. STUDY DESIGN: Suitable mandibular STIR imaging conditions were determined by varying inversion time and repetition time in each sequence. STIR magnetic resonance images of 162 healthy subjects and STIR and T1- and T2-weighted spin-echo images of 21 subjects with mandibular osteomyelitis were evaluated. RESULTS: In STIR imaging, the signal of oil was suppressed at an inversion time equaling 100 milliseconds and a repetition time equaling 1500 to 3000 milliseconds. In healthy subjects, the mandibular marrow was revealed to have high signal intensities (100%) and cortical bone had no signal intensities (100%) on STIR images. In surrounding soft tissue in these healthy subjects, the submandibular glands were shown to have high signal intensities (100%); the parotid glands had intermediate to high signal intensities (100%); the sublingual glands had high (88.9%) and intermediate to high (11.1%) signal intensities; lymph nodes had high signal intensities (100%); and the masseter muscles had intermediate signal intensities (100%) on STIR images. The lesions in bone marrow had low (75%) and low to intermediate (25%) signal intensities on T1-weighted images and high (54%), intermediate to high (29%), and intermediate (17%) signal intensities on T2-weighted images. On STIR images, the signal intensities resulted in high (75%), intermediate to high (21%), and intermediate (4%) signal intensities. CONCLUSIONS: STIR imaging is highly effective for the evaluation of bone marrow and surrounding soft tissue in terms of the detection of osteomyelitis in the mandible and the identification of inflammation spreading to soft tissue.

Adult↗

Comparison between manual and automatic segment generation in step-and-shoot IMRT of prostate cancer.

PURPOSE: To compare two methods to generate treatment plans for intensity-modulated radiotherapy (IMRT) of prostate cancer, delivered in a step-and-shoot mode. The first method uses fluence optimization (inverse planning) followed by conversion of the fluence weight map into a limited number of segments. In the second method, segments are manually assigned using a class solution (forward planning), followed by computer optimization of the segment weights. METHODS: Treatment plans for IMRT, utilizing a simultaneous integrated boost, were created. Plans comprise a five-field technique to deliver 78 Gy to the prostate plus seminal vesicles. Five patients were evaluated. Optimization objectives of both planning approaches concerned dose coverage of the target volumes and the dose distribution in the rectal wall. The two methods were evaluated by comparing dose distributions, the complexity of the resulting plan and the time expenditure to generate and to deliver the plan. RESULTS: For both planning approaches 99% of the target volumes received 95% of the prescribed dose, which complies with our planning objectives. Inverse planning resulted in more conformal dose distributions than forward planning (conformity index: 1.37 versus 1.51). Inverse planning reduced the dose to the rectal wall compared to a manually designed plan, albeit to a small extent. The theoretical probability of severe rectal proctitis and/or stenosis was reduced on average by 1.9% with inverse planning. Maximal sparing of the rectal wall was achieved with inverse planning for a patient whose target volume was partly wrapped around the rectum. The number of segments generated with inverse planning ranged between 33 and 52, and between 9 and 13 segments for manually created segments. CONCLUSION: Dose coverage of the planning target volumes is adequate for both approaches of planning. Inverse planning results in slightly better dose distributions with respect to the rectal wall compared to manual planning, at the cost of an increase of the number of segments by a factor of 3.

Humans↗

Linoleic acid and risk of sudden cardiac death.

OBJECTIVE: To test the hypothesis that the essential fatty acid, linoleic acid, measured in adipose tissue as an indicator of long term dietary intake, is inversely related to the risk of sudden cardiac death. DESIGN: A population case-control study. SETTING: A regional health district. SUBJECTS: 84 men (age 25-64 years) who died instantaneously or within 24 hours of the onset of symptoms with no history of coronary heart disease or medically treated hyperlipidaemia, and in whom coronary artery disease was diagnosed at postmortem examination as the primary cause of death, were compared with 292 age (to within two years) and sex matched healthy controls and their partners drawn from the general practitioners' records with whom the cases were registered. MAIN OUTCOME MEASURES: Fatty acid composition of adipose tissue and the risk of sudden cardiac death. RESULTS: Linoleic acid in adipose tissue was inversely related to the risk of sudden cardiac death. The estimated relative risk (95% CI) of sudden cardiac death was 5.7 (1.8 to 17.9) for the lowest quintile and 4.0 (1.2 to 12.9) for the next quintile of adipose linoleic acid in the control population when compared with the highest quintile. This inverse relation was independent of age, reported smoking habits, history of hypertension, and diabetes, although there was a close association with cigarette smoking. The estimated adjusted proportionate increase in risk (95% CI) of sudden cardiac death was 1.14 (1.03 to 1.23) for every 1% reduction of linoleic acid in adipose tissue. CONCLUSIONS: The percentage content of linoleic acid in adipose tissue was inversely related to the risk of sudden cardiac death. Populations with a high risk of sudden cardiac death may benefit from increasing their dietary intake of polyunsaturated fatty acid oils, principally from cereals and vegetables.

Adipose Tissue↗

Internal porosity of cast titanium removable partial dentures: influence of sprue direction and diameter on porosity in simplified circumferential clasps.

OBJECTIVE: The behavior of molten titanium in molds of complicated shape is still insufficiently understood; consequently, definite spruing criteria are not yet available for titanium RPD frameworks. This study investigated the influence of sprue design on porosity in pressure-cast titanium circumferential clasps. METHODS: The patterns of 90 circumferential clasps were sprued with three directions (0, 30 and 60 degrees , as measured between the sprue and the symmetry plane of the clasp assembly) and three sprue diameters (1.5, 2.0 and 2.5mm). CPTi was cast in a one-chamber pressure casting machine. Pore number and size were assessed on radiographs of the castings. Statistical analysis was done by two-way analysis of variance (ANOVA), followed by Fisher's PLSD post hoc test. RESULTS: The porosity in lingual arms increased significantly with increase of sprue diameter and sprue angle, while the porosity in minor connectors had an inversely proportional distribution. Very low porosity, uninfluenced by sprue design, was found in buccal arms. In conclusion, internal porosity in titanium circumferential clasp arms can be minimized through sprue design: the 0 degrees sprue direction produced the least porosity, while for the 30 and 60 degrees directions, 1.5mm diameter sprues produced lower porosity than 2.0 and 2.5mm diameter sprues. SIGNIFICANCE: In this study, the lowest porosity in titanium circumferential clasp arms was obtained with sprues attached perpendicularly to the minor connectors, regardless of sprue diameter. Conventional sprue directions produced significantly higher porosity in clasp lingual arms, the amount of porosity increasing with sprue diameter.

Analysis of Variance↗

Design, construction and performance of the most efficient biomass producing E. coli bacterium.

Inverse metabolic engineering based on elementary mode analysis was applied to maximize the biomass yield of Escherchia coli MG1655. Elementary mode analysis was previously employed to identify among 1691 possible pathways for cell growth the most efficient pathway with maximum biomass yield. The metabolic network analysis predicted that deletion of only 6 genes reduces the number of possible elementary modes to the most efficient pathway. We have constructed a strain containing these gene deletions and we evaluated its properties in batch and in chemostat growth experiments. The results show that the theoretical predictions are closely matched by the properties of the designed strain.

Biomass↗